Biofilm formation in trimethoprim/sulfamethoxazole-susceptible and trimethoprim/sulfamethoxazoleresistant uropathogenic Escherichia coli

Objective: To compare bioi lm formation in trimethoprim/sulfamethoxazole(SXT)-susceptible Escherichia coli(E. coli)(SSEC) and SXT-resistant E. coli(SREC) isolated from patients with urinary tract infections, and study the motile ability and physical characteristics of the isolates.Methods: A total of 74 E. coli isolates were tested for antimicrobial susceptibility with the disc diffusion assay. Based on the SXT-susceptibility test, the E. coli isolates were divided into SSEC(N = 30) and SREC(N = 44) groups. All E. coli isolates were examined for motile ability by using a motility test medium, and for checking bioi lm formation a scanning electron microscope was used. Bacterial colony size was measured with a vernier caliper and bacterial cell length was measured under a light microscope. The bacterial growth rate was studied by plotting the cell growth(absorbance) versus the incubation time. Results: The frequencies of non-motility and biofilm formation in the SREC group were signii cantly higher than that in the SSEC group(P < 0.01). The SREC bacterial cell length was shorter than that in the SSEC group [(1.35 ± 0.05) vs.(1.53 ± 0.05) μm, P < 0.05)], whereas the bacterial colony size and mid-log phase of the growth curve were not signii cantly dif erent. Conclusions: The present study indicated that bioi lm formation and phenotypic change of uropathogenic E. coli can be attributed to the mechanism of E. coli SXT resistance.

Responses of soil enzyme and microbial community under co-loading of different microplastics and sulfamethoxazole

Polyamide/polyethylene(PA/PE)microplastics were injected into soil containing sulfamethoxazole(SMX)to investigate their combined effects on SMX removal,soil enzyme activity,and microbial communities.The results show that both PA and PE transiently increase SMX removal and inhibite the stimulation of microbial species diversity by SMX.The effect of PE is more significant.Meanwhile,PE combined with SMX increases the relative abundances of Actinobacteria and Pseudomonas,while PA combined with SMX decreases the relative abundances of Nocardioides and Streptomyces.In addition,PA/PE combined with SMX can increase dehydrogenase,urease,ammonia monooxygenase,and nitrate reductase activities in the soil while inhibiting the activity of laccase.Compared with PA combined with SMX,the activities of dehydrogenase,urease,ammonia monooxygenase,and laccase of PE combined with SMX increase by 9.82%,10.41%,8.07%,and 5.47%,while the activities of nitrate reductase and neutral phosphatase decrease by 1.47%and 6.78%.

Degradation of sulfamethoxazole in water by dielectric barrier discharge plasma jet:influencing parameters,degradation pathway,toxicity evaluation

Sulfamethoxazole(SMX)is an antibiotic and widely present in aquatic environments,so it presents a serious threat to human health and sustainable development.A dielectric barrier discharge(DBD)plasma jet was utilized to degrade aqueous SMX,and the effects of various operating parameters(working gas,discharge power,etc)on SMX degradation performance were studied.The experimental results showed that the DBD plasma jet can obtain a relatively high degradation efficiency for SMX when the discharge power is high with an oxygen atmosphere,the initial concentration of SMX is low,and the aqueous solution is under acidic conditions.The reactive species produced in the liquid phase were detected,and OH radicals and O3were found to play a significant role in the degradation of SMX.Moreover,the process of SMX degradation could be better fitted by the quasi-first-order reaction kinetic equation.The analysis of the SMX degradation process indicated that SMX was gradually decomposed and 4-amino benzene sulfonic acid,benzene sulfonamide,4-nitro SMX,and phenylsulfinyl acid were detected,and thus three possible degradation pathways were finally proposed.The mineralization degree of SMX reached 90.04%after plasma treatment for 20 min,and the toxicity of the solution fluctuated with the discharge time but eventually decreased.

Analysis of the Effectiveness of Biling Weitong Granules Combined with Trimethoprim and Vonoprazan in The Treatment of Reflux Esophagitis

Objective:To analyze the effectiveness of Biling Weitong Granules(BLWTG)combined with trimethoprim and vonoprazan in treating reflux esophagitis.Methods:Sixty patients with reflux esophagitis admitted to our hospital from March 2020 to March 2023 were selected as study subjects and randomly divided into a control group and an experimental group,with 30 cases in each group.The control group received only the combination treatment of trimethoprim and vonoprazan,while the experimental group was treated with BLWTG based on the control group.The acid reflux and heartburn symptom scores,quality-of-life scores,clinical efficacy,Chinese medicine symptom incidences,and the occurrence of adverse reactions before and after treatment in the two groups were compared.Results:After treatment,the acid reflux and heartburn symptom scores of patients in the experimental group were lower than those of the treatment control group,and the quality-of-life scores were higher than those of the treatment control group(P<0.05).The total clinical efficacy of the experimental group was 96.66%,which was significantly higher than that of the control group(73.33%,P<0.05).After treatment,the incidence of Chinese medicine symptoms,such as nausea and vomiting,abdominal distension and abdominal pain,and loss of appetite of the patients in the experimental group were significantly lower than those of the control group(P<0.05).During the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,which indicated that the safety of the two treatments was comparable(P>0.05).Conclusion:BLWTG combined with trimethoprim and vonoprazan was safe and reliable in treating reflux esophagitis,effectively relieving the symptoms and improving its clinical efficacy.This treatment is worthy of popularization.

Antimicrobial therapy using sulfamethoxazole trimethoprim for Kawasaki disease patients unresponsive to intravenous immunoglobulin

Our previous study suggested that the production of superantigens and heat-shock protein 60 by small intestinal bacteria might play a role in Kawasaki disease (KD). We demonstrated that they were all resistant to commonly used antibiotics, except for sulamethoxazole trimethoprim (SMX-TMP). We used SMX-TMP for 7 cases of KD that were unresponsive to intravenous immunoglobulin (IVIG) and studied the antipyretic potency of this treatment. In 6 out of the 7 cases, we demonstrated that antipyretic potency was observed without side effects within 2 days of the initial administration. Antimicrobial therapy using SMX-TMP might represent a novel strategy for cases of KD that are unresponsive to IVIG.

A Patient with Acute Liver Injury after Sulfamethoxazole/Trimethoprim Treatment for Pyelonephritis

Background: Sulfamethoxazole/Trimethoprim is a commonly used drug in a variety of clinically indicated scenarios, but it is not without side effect. Case-reports have stated that adverse reactions secondary to Sulfamethoxazole/Trimethoprim can present very early in the course of treatment, especially in patients who have a higher predisposition. Thus, the burden is placed on the clinician to be wary of these side effects and be able to recognize them in the correct clinic scenario. Objective: To discuss the risk of developing cholestatic hepatic dysfunction secondary to treatment with sulfamethoxazole/trimethoprim. Methods: We present the history, physical findings, laboratory investigations, and clinical course of a 47-year-old African-American female who developed cholestatic hepatic dysfunction after treatment with sulfamethoxazole/trimethoprim for pyelonephritis. Results: Drug-induced liver injury is a rare complication of sulfamethoxazole/trimethoprim therapy and only 20% of cases are secondary to cholestatic hepatic dysfunction. Our patient, who had been on sulfamethoxazole/trimethoprim for 7 days for pyelonephritis, presented to our hospital with a clinical picture consistent with hepatic injury;her laboratory investigations were noteworthy for an elevated white blood cell count, platelet count, and elevated transaminases, along with alkaline phosphatase levels greater than 2 times the upper limit of normal. Promptly following the discontinuation of sulfamethoxazole/trimethoprim, our patient improved clinically and her liver enzymes down-trended during the course of her hospital stay. She returned to normal at her 4 month follow up, thus confirming the diagnosis of cholestatic hepatic dysfunction secondary to sulfamethoxazole/trimethoprim. Conclusion: Cholestatic hepatic dysfunction is a form of drug-induced liver injury and a rare complication of sulfamethoxazole/trimethoprim treatment. The majority of cases resolve following discontinuation of the offending medication. However, a small percentage of patients may progress to liver failure and ultimately require liver transplantation. Clinicians should be aware of these risks to avoid delaying the discontinuation of sulfamethoxazole/trimethoprim.

Comparative Study of the Mutant Prevention Concentrations of Sulfamethoxazole-Trimethoprim Alone and in Combination with Levofloxacin against <i>Stenotrophomonas maltophilia</i>

Objectives: To determine the mutant prevention concentration (MPC) of sulfamethoxazole-trimethoprim (SXT) alone and in combination with levofloxacin (LVX) against Stenotrophomonas maltophilia (S. maltophilia) and to determine if the combination may decrease the emergence of resistant mutants. Methods: The MPC with 20 S. maltophilia strains which were both susceptible to SXT and LVX were determined by inhibiting visible growth among 1010 CFU on four agar plates after 72 hours incubation at 37°C. Results: All except two strains (18/20) showed a mutant prevention concentration ≥ 152/8 μg/mL for SXT and the range of the mutant prevention concentration for the SXT in combination with LVX is 9.5/0.5~608/32 μg/mL, which demonstrates at least 2 fold reduction except one strain. There was a significant difference (P < 0.01) between SXT alone and in combination with LVX on the mutant prevention concentration and mutant prevention concentration/minimum inhibitory concentration values. Conclusions: The MPC/MIC values were narrowed for SXT by combining with LVX against the S maltophilia. The combination may decrease the enrichment of mutant bacterial populations. Much study is needed to verify whether the using of drug combinations may restrict or even block the selection of S. maltophilia mutants.

Trimethoprim-Sulfamethoxazole-Induced Hepatitis in Mixed Connective Tissue Disease

Trimethoprim-Sulfamethoxazole (TMP-SMZ) is associated with severe hepatic toxicity or liver failure. We present a case of severe hepatic toxicity for whom TMP-SMZ was prescribed as part of treatment for mixed connective tissue disease (MCTD). TMP-SMZ was used to prevent complications from steroid therapy, but fever and hepatic toxicity developed with repeated TMP-SMZ medication. While the drug lymphocyte stimulation test (DLST) for TMP-SMZ showed negative, the genotype for N-acetyltransferase 2 (NAT2) showed type *6/*7, which is the slow acetylating type for NAT2 activity. This finding for NAT2 genotype and the patient’s clinical history lead us to speculate that her fever and hepatic toxicity were caused by TMP-SMZ.

Sulfamethoxazole-Trimethoprim-Induced Rhabdomyolysis in an Immunocompetent Patient: A Case Report

Sulfamethoxazole-trimethoprim (TMP-SMX)-induced rhabdomyolysis is a rare complication of a commonly used antibiotic. This is a case report of a 43-year old immunocompetent African American woman with a history of depression and chronic alcohol consumption who presented to the emergency department (ED) with worsening bilateral leg pain. Before presentation, the patient was prescribed a twice daily dose of TMP-SMX for a urinary tract infection. The patient reported the development of intensifying leg pain after taking five doses of TMP-SMX. On presentation to the ED she was hemodynamically stable, afebrile, and leg pain intensity 10 out of 10. The patient admitted to daily alcohol consumption and taking vortioxetine 10 mg per day for treatment of depression. Initial labs drawn in the ED showed an elevated creatine kinase (CK) of 26,231 U/L and a normal serum creatinine (SCr) of 1 mg/dL. Through patient history and laboratory tests, common causes of rhabdomyolysis were ruled out. Treatment was initiated with IV fluids plus thiamine and folic acid supplementation, TMP-SMX was discontinued, and vortioxetine 10 mg per day was continued until hospital day five. The patient began to show improvement in lower extremity pain and tenderness and was discharged on hospital day eight with minimal residual leg pain and a CK of 2809 U/L. This case report presents only the third incidence of an immunocompetent patient developing TMP-SMX-induced rhabdomyolysis. This case highlights an opportunity for a pharmacist’s intervention and the need for future research to determine risk factors of TMP-SMX-induced rhabdomyolysis in immunocompetent patients.

Development of Surface Plasmon Resonance-Based Biosensor Immunoassay for Sulfamethoxazole

The illegal use of veterinary drugs has led to the occurrence of residues in food of animal origin.This is a hazard to people's health.In this paper,a sensitive and fast assay was developed to determine sulfamethoxazole (SMOZ) in PBS with a homemade surface plasmon resonance (SPR)-based biosensor which had a single flow channel and two references.The derivative of SMOZ was covalently immobilized to a carboxymethyldextran modified gold film.A recently developed monoclonal antibody against sulfamethoxazole was used to develop an inhibitive immunobiosensor assay in which the antibody was mixed with SMOZ of different concentrations prepared with PBS to construct a standard curve with a low limit of detection(LOD).The effect of matrix in milk was also studied.Calculating of the apparent concentration showed the cross-reactivity with other sulfonamides.

Non-covalent binding analysis of sulfamethoxazole to human serum albumin:Fluorescence spectroscopy,UV-vis,FT-IR,voltammetric and molecular modeling

This study was designed to examine the interaction of sulfamethoxazole （SMZ） with human serum albumin（HSA）. Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of human serum albumin by SMZ was static mechanism. The binding constant values for the SMZ-HSA system were obtained to be 22,500 L/mol at 288 K, 15,600 L/mol at 298 K, and 8500 L/mol at 308 K. The distance r between donor and acceptor was evaluated according to the theory of Foster energy transfer. The results of spectroscopic analysis and molecular modeling techniques showed that the conformation of human serum albumin had been changed in the presence of SMZ. The thermodynamic parameters, namely enthalpy change （ΔH^0） - 36.0 kJ/mol, entropy change （ΔS^0） - 41.3 Jim01 K and free energy change （ΔG^0） - 23.7 kJ/ mol, were calculated by using van＇t Hoff equation. The effect of common ions on the binding of SMZ to HSA was tested.

Preparation of Molecularly Imprinted Composites Initiated by Hemin/Graphene Hybrid Nanosheets and Its Application in Detection of Sulfamethoxazole

Molecularly imprinted polymers(MIPs)exhibit high selectivity resulting from imprinted cavities and superior performance from functional materials,which have attracted much attention in many fields.However,the combination of MIPs film and functional materials is a great challenge.In this study,hemin/graphene hybrid nanosheets(H-GNs)were used to initiate the imprinted polymerization by catalyzing the generation of free radicals.Thus,MIPs using sulfamethoxazole as the template was directly prepared on the surface of H-GNs without any film modification.Most importantly,the template could be absorbed on the H-GNs to enhance the number of imprinted sites per unit surface area,which could improve the selectivity of MIPs film.Thus,the composites could exhibit high adsorption capacity(29.4 mg/g),imprinting factor(4.2)and excellent conductivity,which were modified on the surface of electrode for rapid,selective and sensitive detection of sulfamethoxazole in food and serum samples.The linear range was changed from 5μg/kg to 1 mg/g and the limit of detection was 1.2μg/kg.This sensor was free from interference caused by analogues of sulfamethoxazole,which provides a novel insight for the preparation of MIPs-based sensor and its application in food safety monitoring and human exposure study.

Pharmacokinetics and acetylation of sulfamethoxazole in turbot Scophthalmus maximus after intravascular administration

The pharmacokinetic profi les and sulfamethoxazole(SMX) acetylation process in turbot reared at 18°C were investigated. Either SMX(parent drug) or its acetylized metabolite, N4-acetylsulfamethoxazole(Ac SMX), was administered intravascularly to turbot at a dosage of 50 mg/kg BW. Serum concentrations of the parent drug and its metabolite were both measured by HPLC, and the changes in concentration over time were analyzed in two- and non-compartment models because SMX treatment produced multiple peaks. The results demonstrated that the elimination half-life of the parent drugs, SMX and Ac SMX, were 159.2 and 5.9 h, respectively. The apparent volume of distribution was 0.2 and 0.8 L/kg, and the clearance was 0.038 and 0.222 L/(h·kg), for SMX and Ac SMX, respectively. SMX acetylation in turbot was 2.8%, and the deacetylation of Ac SMX was 0.2%. These fi ndings may be useful in optimizing SMX dosage regimens in turbot aquaculture.

Salt-tolerant Microbiota Enhancing Contaminants Removal from Mariculture Wastewater Containing Sulfamethoxazole in an A/O-MBBR

The wide application of antibiotics in aquaculture requires an efficient treatment of the wastewater before discharging it into the environment.During the wastewater treatment,the influence of antibiotics on the performance of bioreactor should be well revealed due to their toxicity to the functional microbial community.In this study,the effect of feeding 10-30 mg L−1 sulfamethoxazole(SMX)in influent on the performance of an anoxic/oxic-moving bed biofilm reactor(A/O-MBBR)treating mariculture wastewater and the responding change of biofilm microbial communities was investigated.The COD average removal rate remained at 94.61%-97.34%with the dosage of SMX.Compared with that,the nitrifying removals of NH4+-N and NO2−-N were violently inhibited by 30 mg L−1 SMX and denitrifying removal of the NO3−-N decreased obviously with 20 mg L−1 or more SMX.The microbial community in the successful startup bioreactor was relatively abundant,while the diversity of microbial community decreased with the increase of feeding SMX.The salt-tolerant and SMX-resistant genera Arcobacter,Thiothrix,Desulfuromusa and Nitrosomonas were gradually enriched and finally played a vital role in converting COD and recycling nitrogen and sulfur.Hence,the present A/O-MBBR reactor with the salt-tolerant functional microbiota achieved efficient removal of pollutants in the presence of low concentration(e.g.,10 mg L−1)SMX.

Imaging Array SPR Biosensor Immunoassays for Sulfamethoxazole and Sulfamethazine

A homemade array surface plasmon resonance （SPR）-based imaging biosensor was used to develop sensitive and fast immunoassays to determine sulfamethoxazole （SMOZ） and sulfamethazine （SMT） in buffer. Two conjugations of sulfonamide-bovine serum albumin （BSA） were separately immobilized on two different rows of the array chip with one row as reference. The immobilization was carried out in the instrument to monitor the quantity of the conjugations immobilized. The antibody mixed with the sulfonamide in the buffer was injected over the surface of the chip to get a relative response which was inversely proportional to the concentration of the sulfonamide in the PBS buffer. Two calibration curves were constructed and the limit of detection for sufamethoxazole in buffer was 3.5 ng/mL and for sulfamethazine 0.6 ng/mL. The stability and specificity of the antibody were also studied. The monoclonal antibody did not bind with BSA.

A novel indirect inhibitive immunoassay for sulfamethoxazole

A new indirect inhibitive immunoassay using surface plasmon resonance（SPR） coupled with molecularly imprinted polymer（MIP） was developed.A sulfamethoxazole（SMX） MIP coating capillary was produced and used as an in-tube solid phase extraction（SPE） device.The MIP coating formed a nanometer film on the inner wall of the capillary.The anti-SMX mono-antibody was inhibited by SMX extracted by the MIP coating in a dose-dependent manner.The calibration curve was generated by linear fit over the range of 0.04-10.00 ng/mL.The limit of detection was 0.01 ng/mL.This method has high sensitivity and can be performed automatically.

Adsorption of Sulfamethoxazole on Nanoporous Carbon Derived from Metal-Organic Frameworks

Nanoporous Carbon (NPC) with high surface area of 1379 M2/G and high proportion of micropore and mesopore volume of 2.90 Cm3/G was prepared by carbonization of metal?organic frameworks ZIF-8. The adsorption of NPC towards the representative sulfonamide antibiotics sulfamethoxazole (SMX) from aqueous solutions was explored, in comparison with powder active carbon (AC). The adsorption kinetics and isotherms showed that the maximum adsorption capacity (Qm) of NPC toward SMX was 757 Mg/G, around 2 times than that of AC adsorption. The high adsorption affinity of NPC was related to the high surface area and special Mic/Mesopore structure. The pore-filling mechanism as well as electrostatic interaction had important influence on the high adsorption of NPC. The results implied that nanoporous carbon derived from mofs could remove the contaminants from aqueous solutions effectively, and would be a promising adsorbent for the removal of contaminants in the future.

Nitrogen Removal Performance of Denitrifying Ammonium Oxidation System in Treating Sulfamethoxazole-laden Secondary Wastewater Effluent

In this study,nitrogen removal performance of the denitrifying ammonium oxidation(DAO)process was investigated when treating sulfamethoxazole(SMX)-laden secondary wastewater effluent.The influent SMX concentration showed negligible effect on efficiencies for removal of nitrate and COD.However,the ammonium ions removal rate was moderately reduced,when the influent SMX concentration in wastewater reached 6 mg/L.Total nitrogen removal efficiency remained as high as 76.77%towards the day 158 at the end of experiment.Candidatus_Brocadia and Candidatus_Kuenenia were the functional anammox strains.The unclassified_f__Rhodobacteraceae sp.was predominant heterotrophic denitrifying strain in the studied reactor.The concentrations of soluble extracellular polymeric substances in sludge obviously increased from 16.76 mg/g VSS to 32.31 mg/g VSS,which might protect the nitrogen removal strains from high-concentration SMX.This result provides a theoretical and technical foundation for the application of denitrifying ammonium oxidation process in treating sulfamethoxazole-laden secondary wastewater effluent.

1例类鼻疽脓毒症患者的全程个体化药学监护

目的为类鼻疽脓毒症(MS)抗菌药物治疗方案的调整、不良反应的识别和个体化药学监护提供参考。方法临床药师利用血药浓度和基因检测全程参与1例MS患者强化期和根除期治疗过程。通过测定β-内酰胺类和复方磺胺甲噁唑(TMP/SMZ)血药浓度并计算其药代动力学与药效学(PK/PD)参数,结合文献对MS抗菌药物治疗方案进行调整;同时通过高通量测序检测药物相关基因多态性,对药物不良反应的发生原因进行分析并进行处理。结果临床药师利用血药浓度和基因检测手段,提出了亚胺培南西司他丁钠(IMP)给药剂量调整建议,分析了多种药物不良反应的发生原因;通过测定β-内酰胺类药物和TMP/SMZ血药浓度计算PK/PD靶标,通过查询指南和文献为临床医生解释类鼻疽患者脓毒症期和非脓毒症期状态下的达标情况;利用血药浓度和基因检测分析MS患者神经毒性与IMP cmin的相关性,并发现肾毒性与TMP/SMZ的cmax无关,而与患者饮水量相关。经全程抗菌药物治疗后,患者病情好转出院,不良反应得到有效处理。结论临床药师基于抗菌药物血药浓度和基因检测结果解读情况协助临床医生制定MS治疗方案,并为患者提供全程用药监护,提高了临床药物治疗的安全性和有效性。

Fe^(2+)活化与电絮凝活化PAA对SMX的降解效果研究

文章选用磺胺甲恶唑(SMX)作为研究对象,考察电絮凝活化过氧乙酸(EC/PAA)降解SMX的效果,并对EC/PAA体系的缓冲能力及对SMX降解机理进行探究。结果表明:在初始pH值为7、电解质Na_(2)SO_(4)浓度为50 mmol/L、PAA浓度为10 mg/L、SMX浓度为3 mg/L、初始电流强度为60mA和极板间距为2cm的最佳实验条件下,EC/PAA体系20 min内能降解96%的SMX;溶液中共存的H_(2)O_(2)与PAA能够产生协同作用,协同系数SI达到30.125 0。在反应初始pH值为4~8时,反应结束后p H值均可缓冲至7左右,表明该体系具有很好的p H缓冲作用和电絮凝作用;而Fe^(2+)/PAA体系对SMX的降解主要是通过改变溶液pH值进行的,没有缓冲作用。经电子顺磁共振(EPR)鉴别,EC/PAA缓冲体系中的活性物种主要为羟基自由基(·OH)、有机自由基(CH_(3)COO·和CH_(3)COOO·)以及1O2,大部分为·OH,这些自由基共同作用将SMX降解。